The mechanobiology of ageing: reproduction of the ageing and rejuvenating ECM environment

衰老是一个慢性过程，代表着人体的永久和逐渐退化。它可以是生理性的，也可以是病理性的，后者与癌症、糖尿病、阿尔茨海默病和心血管疾病等疾病有关。与衰老相关的病理性或生理性细胞衰退包括细胞和细胞外基质（ECM）的机械性能的退化，以及机械敏感和机械转导信号的改变。机械转导是细胞感知外部机械刺激的能力并将其转化为生化信号，这是许多细胞活动的基础。事实上，机械力是调节基因表达、粘附、迁移和细胞命运的关键，这些都是组织稳态的重要因素，因此，了解多面和时间性衰老过程如何影响这些力传递的途径，对于增强对衰老相关失调和疾病的理解是必要的。该项目旨在研究ECM粘弹特性对细胞衰老的影响，了解细胞在生理和病理衰老过程中如何受到影响，并逆转这一过程，诱导细胞再生。这项工作有两个主要目标：鉴定用于诊断衰老相关疾病的有用生物标志物，并将可能的复原过程定义为预防或治疗病理性衰老的治疗解决方案。与衰老相关的失调

Ageing is a chronic process that represents a permanent and gradual deterioration of the human body. It can be either physiological or pathological, the latter being related to diseases such as cancers, diabetes, Alzheimer's and cardiovascular disease.The pathological or physiological cellular decay associated with ageing includes thedeterioration of mechanical properties of the cell and the extracellular matrix (ECM), and alterations of mechanosensitive and mechanotransductive signalling.Mechanotransduction is the ability of a cell to perceive external mechanical stimuli and translate them into biochemical signals, a phenomenon that is the basis for many cellular activities. Indeed, mechanical forces are pivotal to regulate gene expression, adhesion, migration and cell fate, which are all important factors for tissue homeostasis.Understanding how the multifaced and temporal ageing process affects the pathways involved in the transmission of these forces is, therefore, necessary to enhance the comprehension of ageing-related dysregulation and diseases. The project aims to study the impact of the ECM viscoelastic properties on cellular senescence, either to understand how cells are affected during physiological and pathological ageing and to invert this process inducing the rejuvenation of the cells.This work has two major objectives: identify useful biomarkers for the diagnosis of ageing related diseases and define a possible rejuvenation process as a therapeutical solution to prevent or treat pathological ageing-associated dysregulations.